Health

After a meal, beta cells in the pancreas sense rising blood glucose and release the hormone insulin, which helps the sugar enter cells, where it can be used by the body for energy.

Now researchers at the University of Michigan Life Sciences Institute have uncovered an unexpected mechanism of glucose sensing in skeletal muscles that contributes to the body’s overall regulation of blood sugar levels.

“We found that skeletal muscle cells have machinery to directly sense glucose; in a certain sense it’s like the muscles can taste sugar too,” said senior study author Jiandie Lin, a faculty member at the LSI, where his lab is located.

This ability of muscles to sense blood glucose is a separate and parallel process that augments the insulin-driven response. Together they work as a rheostat to maintain steady glucose levels in the body, particularly after a meal, according to findings published in Molecular Cell.

Continuing to develop this in-depth understanding of how the body self-regulates blood sugar at the molecular level could shed new light on obesity and diabetes, as well as point toward new therapeutic targets, said Zhuoxian Meng, the study’s lead author and a research investigator in Lin’s lab.

The researchers were able to examine the contributions of the glucose-sensing pathway in skeletal muscle by silencing a key gene, BAF60C in cell cultures and in laboratory mice.

“When we did that, the mice lacking BAF60C looked absolutely normal, but after we gave them a high-fat diet to induce obesity, they developed trouble disposing of the additional glucose after a meal,” Lin said. “The well-known insulin mechanism was not sufficient to process the glucose on its own.”

Elevated blood sugar following a meal is a key symptom of Type 2 diabetes. And chronic high blood sugar, also known hyperglycemia, can lead to serious health issues.

“We found that the molecular pathway that’s engaged by glucose in muscle cells, at least the initial steps, is very similar to what happens in the beta cells in the pancreas,” said Lin, who is also a professor of cell and developmental biology at the U-M Medical School. “This is very interesting because there’s a very important class of diabetes drugs known as sulfonylureas that act by closing a potassium channel and causing the beta cells to secrete more insulin.

“Our research shows that this glucose-sensing pathway in muscle cells likely also plays a role in the drugs’ overall glucose-lowering action. The extent of the pathway’s contribution will need to be studied further.”

Additionally, Lin said, there are two steps within the glucose-sensing pathway that could serve as potential targets for modulation with therapeutic compounds.

“It’s amazing how subtle changes in glucose can be detected throughout the body,” Lin said. “Beta cells respond, nerve cells respond, and now we know that muscle cells respond directly, too.”

In January 2016, the EU imposed a maximum limit of inorganic arsenic on manufacturers in a bid to mitigate associated health risks. Researchers at the Institute for Global Food Security at Queen’s have found that little has changed since this law was passed and that 50 per cent of baby rice food products still contain an illegal level of inorganic arsenic.

Professor Meharg, lead author of the study and Professor of Plant and Soil Sciences at Queen’s, said: “This research has shown direct evidence that babies are exposed to illegal levels of arsenic despite the EU regulation to specifically address this health challenge. Babies are particularly vulnerable to the damaging effects of arsenic that can prevent the healthy development of a baby’s growth, IQ and immune system to name but a few.”

Rice has typically, ten times more inorganic arsenic than other foods and chronic exposure can cause a range of health problems including developmental problems, heart disease, diabetes and nervous system damage.

As babies are rapidly growing they are at a sensitive stage of development and are known to be more susceptible to the damaging effects of arsenic, which can inhibit their development and cause long-term health problems. Babies and young children under the age of five also eat around three times more food on a body weight basis than adults, which means that relatively, they have three times greater exposures to inorganic arsenic from the same food item.

The research findings, published in the PLOS ONE journal today, compared the level of arsenic in urine samples among infants who were breast-fed or formula-fed before and after weaning. A higher concentration of arsenic was found in formula-fed infants, particularly among those who were fed non-dairy formulas which includes rice-fortified formulas favoured for infants with dietary requirements such as wheat or dairy intolerance. The weaning process further increased infants’ exposure to arsenic, with babies five times more exposed to arsenic after the weaning process, highlighting the clear link between rice-based baby products and exposure to arsenic.

In this new study, researchers at Queen’s also compared baby food products containing rice before and after the law was passed and discovered that higher levels of arsenic were in fact found in the products since the new regulations were implemented. Nearly 75 per cent of the rice-based products specifically marketed for infants and young children contained more than the standard level of arsenic stipulated by the EU law.

Rice and rice-based products are a popular choice for parents, widely used during weaning and to feed young children, due to its availability, nutritional value and relatively low allergic potential.

Professor Meharg explained: “Products such as rice-cakes and rice cereals are common in babies’ diets. This study found that almost three-quarters of baby crackers, specifically marketed for children exceeded the maximum amount of arsenic.”

Previous research led by Professor Meharg highlighted how a simple process of percolating rice could remove up to 85 per cent of arsenic. Professor Meharg adds: “Simple measures can be taken to dramatically reduce the arsenic in these products so there is no excuse for manufacturers to be selling baby food products with such harmful levels of this carcinogenic substance.

“Manufacturers should be held accountable for selling products that are not meeting the required EU standard. Companies should publish the levels of arsenic in their products to prevent those with illegal amounts from being sold. This will enable consumers to make an informed decision, aware of any risks associated before consuming products containing arsenic.”

Results from a clinical review published in The Journal of the American Osteopathic Association find nearly 1 billion people worldwide may have deficient or insufficient levels of vitamin D due to chronic disease and inadequate sun exposure related to sunscreen use.

The study also found that 95 percent of African American adults may have vitamin D deficiency or insufficiency. Vitamin D variations among races are attributed to differences in skin pigmentation.

“People are spending less time outside and, when they do go out, they’re typically wearing sunscreen, which essentially nullifies the body’s ability to produce vitamin D,” said Kim Pfotenhauer, DO, assistant professor at Touro University and a researcher on this study. “While we want people to protect themselves against skin cancer, there are healthy, moderate levels of unprotected sun exposure that can be very helpful in boosting vitamin D.”

Dr. Pfotenhauer also said chronic diseases like Type 2 Diabetes and those related to malabsorption, including kidney disease, Crohn’s and celiac disease greatly inhibit the body’s ability to metabolize vitamin D from food sources.

Considered a hormone rather than a vitamin, vitamin D is produced when skin is exposed to sunlight. Vitamin D receptors are found in virtually every cell in the human body. As a result, it plays a wide role in the body’s functions, including cell growth modulation, neuromuscular and immune function and inflammation reduction.

Symptoms for insufficient or deficient vitamin D include muscle weakness and bone fractures. People exhibiting these symptoms or who have chronic diseases known to decrease vitamin D, should have their levels checked and if found to be low, discuss treatment options. However, universal screening is likely neither necessary nor prudent absent significant symptoms or chronic disease.

Increasing and maintaining healthy vitamin D levels can be as easy as spending 5-30 minutes in midday sun twice per week. The appropriate time depends on a person’s geographic location and skin pigmentation; lighter skin synthesizes more vitamin D than darker skin. It is important to forgo sunscreen during these sessions because SPF 15 or greater decreases vitamin D3 production by 99 percent.

“You don’t need to go sunbathing at the beach to get the benefits,” said Dr. Pfotenhauer. “A simple walk with arms and legs exposed is enough for most people.”

Food sources such as milk, breakfast cereals and Portobello mushrooms are also fortified with vitamin D. Dr. Pfotenhauer said supplements are a good option, as they are effective and pose few risks, provided they are taken as directed and a physician is consulted beforehand.

Research is ongoing to determine whether vitamin D deficiency has a role in multiple sclerosis, autoimmune disorders, infections, respiratory disease, cardiometabolic disease, cancer and fracture risk.

“Science has been trying to find a one-to-one correspondence between vitamin D levels and specific diseases,” said Dr. Pfotenhauer. “Given vitamin D’s ubiquitous role in the body, I believe sufficient vitamin D is more about overall health. Our job as osteopathic physicians is to recognise those patients that need to be tested and treat them accordingly.”

Currently, insufficiency is defined as between 21 and 30 ng/ml and deficiency is considered below 20ng/ml by the Endocrine Society.

The growth of bacteria can be stimulated by antibiotics, scientists at the University of Exeter have discovered.

The EPSRC-funded researchers exposed E.coli bacteria to eight rounds of antibiotic treatment over four days and found the bug, which can cause severe stomach pain, diarrhea and kidney failure in humans, had increased antibiotic resistance with each treatment.

This had been expected, but researchers were surprised to find mutated E.coli reproduced faster than before encountering the drugs and formed populations that were three times larger because of the mutations.

This was only seen in bacteria exposed to antibiotics and when researchers took the drug away, the evolutionary changes were not undone and the new-found abilities remained.

“Our research suggests there could be added benefits for E.coli bacteria when they evolve resistance to clinical levels of antibiotics,” said lead author Professor Robert Beardmore, of the University of Exeter.

“It’s often said that Darwinian evolution is slow, but nothing could be further from the truth, particularly when bacteria are exposed to antibiotics.

“Bacteria have a remarkable ability to rearrange their DNA and this can stop drugs working, sometimes in a matter of days.

“While rapid DNA change can be dangerous to a human cell, to a bacterium like E.coli it can have multiple benefits, provided they hit on the right changes.”

The researchers tested the effects of the antibiotic doxycycline on E.coli as part of a study of DNA changes brought about by antibiotics.

The E.coli “uber-bug” that subsequently evolved was safely frozen at -80C and the scientists used genetic sequencing to find out which DNA changes were responsible for its unusual evolution.

Some changes are well known and have been seen in clinical patients, like E.coli producing more antibiotic pumps that bacteria exploit to push antibiotics out of the cell.

Another change saw the loss of DNA that is known to describe a dormant virus.

“Our best guess is that losing viral DNA stops the E.coli destroying itself, so we see more bacterial cells growing once the increase in pump DNA allows them to resist the antibiotic in the first place,” said Dr Carlos Reding, who was part of the study.

“This creates an evolutionary force for change on two regions of the E.coli genome.

“Normally, self-destruction can help bacteria colonise surfaces through the production of biofilms. You see biofilms in a dirty sink when you look down the plughole.

“But our study used liquid conditions, a bit like the bloodstream, so the E.coli could give up on its biofilm lifestyle in favour of increasing cell production.”

Dr Mark Hewlett, also of the University of Exeter, added: “It is said by some that drug resistance evolution doesn’t take place at high dosages but our paper shows that it can and that bacteria can change in ways that would not be beneficial for the treatment of certain types of infection.

“This shows it’s important to use the right antibiotic on patients as soon as possible so we don’t see adaptations like these in the clinic.”

A University of Melbourne researcher has found that one-third of Australians report health problems ranging from migraine headaches to asthma attacks, when exposed to common fragranced consumer products such as air fresheners, cleaning products, laundry supplies, and personal care products.

The research was conducted by Anne Steinemann, Professor of Civil Engineering and Chair of Sustainable Cities, from the University of Melbourne School of Engineering and published in the journal Preventive Medicine Reports.

When exposed to fragranced products, 33 per cent of Australians suffer adverse health effects, such as breathing difficulties, headaches, dizziness, rashes, congestion, seizures, nausea, and a range of other physical problems.

The results mirrored those from similar research Professor Steinemann conducted in the United States, which found 34.7 per cent of people experienced health problems when exposed to fragranced products.

“This is an epidemic,” Professor Steinemann said. “Fragranced products are creating health problems across Australia. The effects can be immediate, severe and potentially disabling,” she said. “But they can also be subtle and people may not realise they’re being affected.”

Professor Steinemann conducted a nationally representative population survey in Australia, using a random sample of 1098 people from a large, web-based panel held by Survey Sampling International (SSI).

The research found 7.7 per cent of Australians have lost workdays or a job in the past year due to illness from fragranced product exposure in the workplace, and 16.7 per cent want to leave a shop or business as quickly as possible if they smell air fresheners or other fragranced products.

Professor Steinemann’s previous research showed fragranced products emit a range of chemicals, including hazardous air pollutants, but ingredients do not need to be fully disclosed on the product label or safety data sheet.

“All types of fragranced products tested, even those with claims of ‘green,’ ‘organic,’ and ‘all-natural’, emitted hazardous air pollutants,” she said.

Her research continues to investigate why fragrance chemicals are causing health problems and the implications for indoor environments. “As my study found, about twice as many Australians would prefer that workplaces, health care facilities and professionals, hotels, and aeroplanes were fragrance-free rather than fragranced,” said Professor Steinemann.

A City of Hope-led study found that the use of low-dose aspirin (81mg) reduces the risk of breast cancer in women who are part of the California’s Teacher’s Study. This study, which is the first to suggest that the reduction in risk occurs for low-dose aspirin, was proposed by City of Hope’s Leslie Bernstein, Ph.D., professor and director of the Division of Biomarkers of Early Detection and Prevention, and published online in the journal Breast Cancer Research.

Bernstein and her colleagues saw an overall 16 percent lower risk of breast cancer in women who reported using low-dose aspirin at least three times per week. Such regular use of low-dose aspirin reduced the risk by 20 percent of estrogen or progesterone receptor positive, HER2 negative breast cancer, which is the most common breast cancer subtype.

“The study found an interesting protective association between low-dose aspirin and breast cancer,” said lead author Christina A. Clarke, Ph.D., M.P.H., from the Cancer Prevention Institute of California. “We did not by and large find associations with the other pain medications like ibuprofen and acetaminophen. We also did not find associations with regular aspirin since this type of medication is taken sporadically for headaches or other pain, and not daily for prevention of cardiovascular disease.”

This study differed from other studies that have looked at aspirin and cancer risk because it focused on the dose levels of the aspirin women had taken and tracked the frequency of the use of low-dose aspirin as opposed to regular aspirin. It was also able to look in detail at subtypes of breast cancer.

“We already knew that aspirin is a weak aromatase inhibitor and we treat women with breast cancer with stronger aromatase inhibitors since they reduce the amount of estrogen postmenopausal women have circulating in their blood,” said Bernstein. “We thought that if aspirin can inhibit aromatase, it ought to reduce the likelihood that breast cancer would develop and it could also be an effective way to improve breast cancer patients’ prognosis once they no longer take the more potent aromatase inhibitors.” Bernstein added, “Aspirin also reduces inflammation, which may be another mechanism by which aspirin taken regularly can lower risk of breast cancer developing or recurring.”

As part of the study, researchers analysed data recorded in questionnaires submitted by 57,164 women in the California’s Teacher’s Study. In 2005, participants answered questions regarding family history of cancer and other conditions, use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS), menstrual and reproductive history, use of hormones, weight and height, living environment, diet, alcohol use and physical activity. In the ensuing years before 2013, 1,457 of these participants developed invasive breast cancer.

The team of researchers chose to focus on low-dose “baby” aspirin, because not only is it inexpensive and readily available as potential means of prevention, but because there are already a lot of people already taking it for prevention of other diseases such as heart disease and even colon cancer.

Now that we have some data separating low-dose from higher-dose aspirin, more detailed research can be undertaken to understand the full value of low-dose aspirin for breast cancer prevention,” said Clarke.”

In humans, developing metabolic disease, particularly type 2 diabetes, is correlated with having bacteria that penetrate the mucus lining of the colon, according to a study led by Drs. Benoit Chassaing and Andrew Gewirtz at Georgia State University.

The findings, which provide insight on how people develop insulin resistance-associated dysglycemia (abnormal blood glucose levels), are published in the journal Cellular and Molecular Gastroenterology and Hepatology.

Metabolic syndrome is the term for a group of factors that raise a person’s risk for heart disease and other health problems, such as diabetes and stroke. Such risk factors include a large waistline, a high triglyceride level (type of fat found in the blood), low HDL cholesterol level, high blood pressure and high fasting blood sugar levels. Metabolic syndrome, which has become far more common due to a rise in obesity rates among adults, is a leading risk factor for many serious, life-threatening diseases, including type 2 diabetes and heart disease, according to the National Institutes of Health.

“Alterations in bacteria have been associated with metabolic diseases, including obesity and type 2 diabetes, but mechanisms remain elusive,” said Gewirtz, professor in the Institute for Biomedical Sciences at Georgia State.

“Previous studies in mice have indicated that bacteria that are able to encroach upon the epithelium might be able to promote inflammation that drives metabolic diseases, and now we’ve shown that this is also a feature of metabolic disease in humans, specifically type 2 diabetics who are exhibiting microbiota encroachment.”

The epithelium is the mucus-lined cellular covering of internal and external surfaces of the body, including the intestinal tract. Gut microbiota is the collective term for the communities of microscopic living organisms that inhabit this environment. Gut microbiota that live in the outer regions of the mucus and remain a safe distance from epithelial cells provide a benefit to the host, but Chassaing and Gewirtz hypothesise that microbiota that encroach upon host cells drive chronic inflammation that interferes with the normal action of insulin, promoting type 2 diabetes.

In this study, the researchers used samples from human subjects enrolled at the Veteran’s Administration Hospital in Atlanta. The subjects, at least 21 years old with no major health problems besides diabetes, were undergoing colonoscopy for colon cancer screening. The researchers obtained each subject’s history of diabetes and gastrointestinal complaints through interviews and reviewing medical records. During the colonoscopy procedure, two mucosal biopsies were taken from the left colon and analysed.

“The data are impressive and may have opened a new field of investigation in metabolic function and type 2 diabetes,” said Dr. Samuel Klein, chief of the Division of Geriatrics and Nutritional Science at the Washington University School of Medicine Diabetes Research Center.

The researchers are conducting follow-up studies to determine the identity of the bacteria that are invading the colon lining and are exploring remedies to prevent such bacteria encroachment.

Chassaing, assistant professor in the Institute for Biomedical Sciences and Center for Inflammation, Immunity and Infection, is lead author of the study.

Co-authors of the paper include Dr. Shreya M. Raja and Dr. Shanthi Srinivasan of Emory University School of Medicine and Dr. James D. Lewis of Perelman School of Medicine at University of Pennsylvania.

The study is funded by the National Institutes of Health and the Crohn’s and Colitis Foundation.

More About Metabolic Syndrome.

A rise in caloric consumption combined with a decrease in physical activity has contributed to a boom of metabolic diseases, such as type 2 diabetes mellitus and cardiovascular diseases (e.g., heart failure and stroke). Over the last couple of decades, studies exploring these diseases have uncovered some of the complex pathophysiological mechanisms involved, resulting in the identification of a plethora of interconnected physiological, pathophysiological, biochemical, and clinical factors that play a role in their development. These factors include obesity/abdominal adiposity, insulin resistance, dyslipidemia, a low-grade state of chronic inflammation, hypoxia, oxidative stress, fasting hyperglycemia, high blood pressure (hypertension), endothelial dysfunction, a hyper-coagulable state, genetics, and more. This constellation of interconnected risk factors that play a role in the development of metabolic and cardiovascular diseases has been dubbed metabolic syndrome.

The concept of this complex syndrome was first introduced by Gerald M. Raven during the Banting Medal Address during the 1988 American Diabetes Association meeting. He proposed that cardiovascular risk was high among insulin-resistant, hyper-insulinemic individuals who were glucose intolerant and who exhibited a collection of other risk factors, such as increased levels of plasma triglyceride, low HDL-cholesterol, and essential hypertension. He called the collection of these factors Syndrome X, as the significance of these abnormalities and their precise role in cardiovascular diseases was not fully understood at the time. While the condition has been given several definitions over the years based on improved understanding, a harmonized definition for metabolic syndrome was the result of a 2009 joint meeting of the American Heart Association, the National Heart Lung and Blood Institute, the International Diabetes Foundation, the World Heart Federation and the International Association for the Study of Obesity. Accordingly, metabolic syndrome is diagnosed based on the presence of any three of five criteria:

• Increased waist circumference (as a measure of abdominal obesity that is specific to populations and ethnic groups);

• Triglycerides levels at 150mg/dl or higher;

• HDL-c levels at 40 mg/dL or lower in men and 50 mg/dL or lower in women;

• Blood pressure at 130/85 or higher; and

• Fasting plasma glucose (glycemia) at 100mg/dL or higher.

Diagnosed with these criteria, metabolic syndrome confers a five-fold increased risk for type 2 diabetes and a three-fold increased risk for cardiovascular disease, including an up to four-fold increased risk for stroke or heart failure. Metabolic syndrome also is associated with several other diseases, including many cancers, polycystic ovarian syndrome, and neurological disorders.

With approximately 35% of all adults and 50% of individuals aged 60 years or older estimated to have metabolic syndrome, it is a major public health issue and is changing what was thought of as a “normal” individual. The presence of metabolic syndrome in an increasing percentage of individuals suggests an altered metabolic, physiological, and pathophysiological state that may change or exacerbate the toxic responses to drugs and/or environmental toxicants. And this syndrome is not limited to the adult population. It increasingly is diagnosed in the paediatric population with a prevalence rate of about 11.9% in overweight children and 29% in obese children.

While several intricate pathways and mechanisms are at play in metabolic syndrome, obesity (abdominal obesity in particular) and insulin resistance are considered to be at the core of this syndrome. For example, a positive energy balance leads to adipose tissue expansion and obesity resulting in consequences, which include the following:

• Infiltration of macrophages and other immune cells into the adipose tissue, giving rise to an inflamed adipose tissue with an increased secretion of pro-inflammatory cytokines and adipokines and a concomitant decrease in the anti-inflammatory adipokine, adiponectin.

• Ectopic deposition of fat in key organs such as the liver, heart, skeletal muscle, and pancreas due to spill over from expanded adipose tissue, resulting in tissue lipotoxicity and consequent inhibition of insulin signaling.

• Binding of circulating free fatty acids to toll receptors on various organs, augmenting inflammatory signaling via the downstream activation of NFκB and JNK pathways resulting in a vicious cycle of inflammation, which further inhibits insulin signaling in these tissues.

• Free fatty acid accumulation in tissues and in its breakdown to intracellular diacylglycerol and ceramide, which interferes with insulin signaling and insulin-stimulated glucose uptake. This accumulation of free fatty acids and its incomplete oxidation mediates mitochondrial dysfunction, which triggers formation of reactive oxygen species that induce oxidative stress, which further impairs mitochondrial function. Increased reactive oxygen species levels also hinder insulin signaling and impair GLUT4 translocation.

A failure of cells to respond to insulin results in the pathological condition of insulin resistance. Insulin, by activating complex signaling pathways involving pI3K/AKT, MAPK, and clb and by binding to transcriptions factors such as FOXO and PPARg, regulates glucose uptake and glucose and lipid metabolism in peripheral tissues. Insulin resistance disrupts these pathways, resulting in hyperglycemia and dyslipidemia. Dyslipidemia also results from the accumulation of free fatty acids in the liver along with insulin-augmented lipogenesis, increasing triglyceride production and release, together with an increased hepatic uptake and renal clearance of HDL-c resulting in a dysregulated lipid profile of low levels of HDL-c and high triglyceride seen in metabolic syndrome. Glucotoxicity and lipotoxicity mediate pancreatic β-cell dysfunction in insulin resistance and hyperinsulinemia. This combination of insulin resistance and hyperinsulinemia, additionally, plays a role in the development of hypertension by tipping the balance between endothelial cell secretion of the vasodilator, NO, and the vasoconstrictor, ET-1.

Although obesity and IR are at the core of the pathophysiological mechanisms of metabolic syndrome, several other factors also are implicated, including dysregulation of the hypothalamic-pituitary-adrenal axis, the renin-angiotensin-aldosterone system, the autonomic nervous system, impact of gut microbiome on metabolism, the cellular and metabolic alterations in response to drugs, alcohol, and environmental toxicants. Both genetic and epigenetic mechanisms are thought to play a role besides environmental and lifestyle causes of MS.

An examination of the metabolic disturbances associated with metabolic syndrome reveals that many of the pathways and mechanisms involved overlap with those affected by drugs and environmental toxicants and can result in similar types of cellular and organ toxicities. It also is conceivable that drug responses and toxicities may be altered in subjects with metabolic syndrome in whom several metabolic and signaling pathways have gone awry.